Linking How The Mechanics Of High Rate And Impulse Of Loading To The Brain Leads To Varying Types And Levels Of Damage To Neuronal Structure And Function.

PI: Pfister, Bryan Proposal: 1706157 Every fifteen seconds, someone suffers a traumatic brain injury (TBI) -- leading to over 5.3 million Americans coping with varying severity of brain injuries. Compared to severe TBI, little is known about the consequences of mild TBI or blast TBI on neuronal function that can then lead to cognitive deficits and changes in behavior. In addition, there is wide variability in patient outcomes after a TBI. Injury severity may in part depend on how the head is hit. Indeed, the mechanical nature of injury to the head varies greatly from motor vehicle accidents, falls, sports, assaults, and exposure to blasts. The cause of TBI has mostly been described in terms of tissue strains due to the brain motion in the skull. Distinctively different biomechanical insults to the head will translate to unique loading and deformation patterns throughout the brain. The project goal is to define how the mechanical loading and deformation of neuronal cells associated with motor vehicle accidents (non-impact) differ from high rate and impulse loading associated with blunt impact (sport concussion) and blast exposure (extreme rate) in terms of the effect on structure and function of neuronal cells. With appropriate models and information establishing how biomechanics plays an important role in neuronal structure and function, the TBI community will be able to replicate injury as needed for their studies in order to better understand various injury outcomes. This research will include the participation of engineering students at all levels, senior capstone design projects, and a summer programs for undergraduate and high school students. The PI prioritizes and has experience with including and accommodating students with disabilities.Compared to severe forms of traumatic brain injury (TBI), little is known about the consequences of mild TBI or blast TBI on cellular properties, neural networks, and behavior -- the dysfunction at the core of cognitive deficits. Mild injuries do not show the overt tissue damage present in severe cases, and diagnoses are often missed or uncertain. The variations in TBI are also an important biomechanical problem. The mechanical nature of injury to the head can vary greatly between motor vehicle accidents, falls, sports, assaults, and exposure to blasts. The project hypothesizes that the magnitude, rate and impulse of the local mechanics each contribute to cause different alterations in neuronal structure and function that underlie the variety of outcomes seen in TBI patients. Neuronal and axon pathology have been well characterized in animal models from large brain deformations that are typically associated with head rotations. Accordingly, the known mechanisms of TBI have mostly been described in terms of tissue strains. Only recently has research begun exploring blunt impact and blast modes of injury, but with little focus on how the associated high rate and impulse loading causes damage at the neuronal level. This project focuses on defining how these vastly different biomechanical loading parameters affect structure and function of the neuron, which may shed light on different mechanisms of injury that may be important to the diversity of patient outcomes in head injury. Defining studies make use of an in vitro, 3D neuronal culture model of blast injury and an established in vitro stretch injury model to replicate strains, rates and impulses of three modes (non-impact, blunt pact and blast exposure) of injury. The specific aims are to: 1) create a dose curve of cell viability to blast exposure (vs. overpressure and impulse) in a 3D in vitro blast model; 2) investigate the importance of high strain rate and impulse loading to alterations in neuronal structure; and 3) investigate the importance of high strain rate and impulse loading on neuronal electrical activity.